Trial Outcomes & Findings for A Open-label Study Investigating the Safety and Tolerability of NPSP558, a Recombinant Human Parathyroid Hormone (rhPTH [1-84]), for the Treatment of Adults With Hypoparathyroidism - A Clinical Extension Study (RACE) (NCT NCT01297309)

Last Updated: 2021-05-25

Results Overview

SAE is an adverse event (AE) that results in death, life threatening, persistent or significant incapacity or substantial disruption of ability to conduct normal life functions, hospitalization or prolongation of existing hospitalization, congenital anomaly or birth defect, important medical events that may not result in death, be life threatening, or require hospitalization. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical or medicinal product. Treatment emergent adverse events (TEAEs) were defined as AEs whose onset occurs, severity worsens or intensity increases after receiving the study medication of this study and \<= 30 days after last dose of study drug.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

51 participants

Primary outcome timeframe

From start of study drug administration up to follow-up (82 months)

Results posted on

2021-05-25

Participant Flow

The study was conducted at 12 study centers in the United States between 06 April 2011 (first participant first visit) and 08 June 2018 (last participant last visit).

A total of 51 participants were enrolled and 49 participants received treatment out of them 37 participants completed the study.

Participant milestones

Participant milestones
Measure	rhPTH(1-84) Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Study STARTED	51
Overall Study Treated	49
Overall Study Started Extension Period	46
Overall Study COMPLETED	37
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Reasons for withdrawal
Measure	rhPTH(1-84) Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Overall Study Eligibility failure	2
Overall Study Screen failure	2
Overall Study Withdrawal by Subject	5
Overall Study Adverse Event	1
Overall Study Investigator Decision	2
Overall Study Death	1
Overall Study Participant not entering extensionperiod	1

Baseline Characteristics

A Open-label Study Investigating the Safety and Tolerability of NPSP558, a Recombinant Human Parathyroid Hormone (rhPTH [1-84]), for the Treatment of Adults With Hypoparathyroidism - A Clinical Extension Study (RACE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	rhPTH (1-84) n=49 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Age, Continuous	48.1 Years STANDARD_DEVIATION 9.78 • n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From start of study drug administration up to follow-up (82 months)

Population: Safety population included all enrolled participants who received at least 1 dose of study drug and had post baseline safety data.

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=49 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) Number of participants with TESAE	13 Participants
Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) Number of participants with TEAE	48 Participants

PRIMARY outcome

Timeframe: Week 52

Population: ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

A responder was defined as a participant who met all of the following 3 criteria at each (1) a greater than (\>) 50% reduction from baseline or less than (\<) 500 milligram (mg) of daily calcium supplementation. (2) a \>50% reduction from baseline or \<0.25 microgram (mcg) of daily calcitriol supplementation. (3) an albumin-corrected total serum calcium concentration that was normalized or maintained compared to the baseline greater than or equal to (\>=) 1.875 millimoles per liter (mmol/L) and not exceeding the Upper Limit of Normal (ULN) values (2.15 to 2.55 mmol/L). End of Treatment (EOT) was defined as the last determination of response or last available measurement during the treatment period. Number of responders with calcium source for citrate and carbonate at week 52 was reported here.

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=47 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Number of Responders With Calcium Source at Week 52 Citrate (Responder)	7 Participants
Number of Responders With Calcium Source at Week 52 Carbonate (Responder)	21 Participants

PRIMARY outcome

Timeframe: EOT (up to 82 months)

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=47 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Number of Responders With Calcium Source at End Of Treatment (EOT) (Up to 82 Months) Citrate (Responder)	7 Participants
Number of Responders With Calcium Source at End Of Treatment (EOT) (Up to 82 Months) Carbonate (Responder)	20 Participants

SECONDARY outcome

Timeframe: Baseline, Week 52 and EOT (up to 82 months)

Population: ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement.

Percent change from baseline of oral calcium supplementation were reported. EOT was defined as the last determination of response or last available measurement during the treatment period.

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=49 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Percent Change From Baseline in Oral Calcium Supplementation at Week 52 and EOT (Up to 82 Months) Percent change from baseline at Week 52	-68.7 % change of oral calcium supplementation Standard Deviation 34.07
Percent Change From Baseline in Oral Calcium Supplementation at Week 52 and EOT (Up to 82 Months) Percent change from baseline at EOT	-39.4 % change of oral calcium supplementation Standard Deviation 107.23

SECONDARY outcome

Timeframe: Baseline, Week 52 and EOT (up to 82 months)

Population: ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement.

Percent change from baseline of oral calcitriol supplementation were reported. EOT was defined as the last determination of response or last available measurement during the treatment period.

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=49 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Percent Change From Baseline in Oral Calcitriol Supplementation at Week 52 and EOT (Up to 82 Months) Percent change from baseline at Week 52	-72.024 %changeoforal calcitriol supplementation Standard Deviation 44.6232
Percent Change From Baseline in Oral Calcitriol Supplementation at Week 52 and EOT (Up to 82 Months) Percent change from baseline at EOT	-73.737 %changeoforal calcitriol supplementation Standard Deviation 39.3461

SECONDARY outcome

Timeframe: Baseline, EOT (up to 82 months)

Population: ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement.

Percent change in ACSC was reported. EOT was defined as the last determination of response or last available measurement during the treatment period.

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=49 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Percent Change From Baseline in Albumin Corrected Total Serum Calcium (ACSC) at EOT (Up to 82 Months)	-0.03 Percent change in ACSC Standard Deviation 0.190

SECONDARY outcome

Timeframe: Baseline, EOT (up to 82 months)

Population: ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement.

Change in 24 hour urine calcium excretion was reported. EOT was defined as the last determination of response or last available measurement during the treatment period.

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=49 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Change From Baseline in 24-Hour Urine Calcium Excretion Through EOT (Up to 82 Months) Baseline	8.92 Millimoles per day (mmol/day) Standard Deviation 5.009
Change From Baseline in 24-Hour Urine Calcium Excretion Through EOT (Up to 82 Months) Change from Baseline at EOT	-2.37 Millimoles per day (mmol/day) Standard Deviation 5.809

SECONDARY outcome

Timeframe: Baseline, EOT (up to 82 months)

Change from baseline in urinary calcium concentration in participants who used at least one calcium-sparing diuretics and participants who not used calcium-sparing diuretics were reported. EOT was defined as the last determination of response or last available measurement during the treatment period.

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=47 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Change From Baseline in 24-hour Urine Calcium Excretion in Participants Who Used Calcium-Sparing Diuretics Through EOT (Up to 82 Months) EOT: Participants used calcium sparing diuretics	-4.07 Millimoles per day (mmol/day) Standard Deviation 6.000
Change From Baseline in 24-hour Urine Calcium Excretion in Participants Who Used Calcium-Sparing Diuretics Through EOT (Up to 82 Months) EOT:Participants without calcium sparing diuretics	-1.79 Millimoles per day (mmol/day) Standard Deviation 5.713

SECONDARY outcome

Timeframe: Baseline, EOT (upto 82 months)

Change in serum calcium concentration of the number of participants who used at least one calcium-sparing diuretics and not used calcium sparing diuretics were reported. EOT was defined as the last determination of response or last available measurement during the treatment period.

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=49 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Change From Baseline in Serum Calcium Concentration in Participants Who Used and Calcium Sparing Diuretics at EOT (Upto 82 Months) EOT: Participants used calcium sparing diuretics	-0.21 Millimoles per liter (mmol/L) Standard Deviation 0.194
Change From Baseline in Serum Calcium Concentration in Participants Who Used and Calcium Sparing Diuretics at EOT (Upto 82 Months) EOT:Participants without calcium sparing diuretics	-0.04 Millimoles per liter (mmol/L) Standard Deviation 0.200

SECONDARY outcome

Timeframe: Baseline, Month 72, EOT (upto 82 months)

Change of serum phosphate from baseline were reported. EOT was defined as the last determination of response or last available measurement during the treatment period.

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=49 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Change From Baseline in Serum Phosphate at Month 72 and EOT (Upto 82 Months) Change from Baseline at Month 72	-0.309 Millimoles per day (mmol/day) Standard Deviation 0.2280
Change From Baseline in Serum Phosphate at Month 72 and EOT (Upto 82 Months) Change from Baseline at EOT	-0.254 Millimoles per day (mmol/day) Standard Deviation 0.2924

SECONDARY outcome

Timeframe: EOT (up to 82 months)

Population: ITT population included participants who received at least one dose of study drug and had at least one efficacy measurement.

The normal range of calcium phosphate product is defined as \<= 4.441 millimoles square per liter square (mmol\^2/L\^2).

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=49 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Number of Participants Who Maintained a Calcium Phosphate Product in A Normal Range at EOT (Up to 82 Months)	49 Count of participants

SECONDARY outcome

Timeframe: Baseline, EOT (up to 82 months)

Bone Turnover Markers such as bone specific alkaline phosphatase (BSAP), serum procollagen type 1 amino-terminal propeptide (P1NP) , osteocalcin were reported in particpiants. EOT was defined as the last determination of response or last available measurement during the treatment period.

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=49 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Change From Baseline in Bone Turnover Markers at EOT (Up to 82 Months) EOT: Bone Specific alkaline phosphatase	5.27 Microgram per liter (μg/L) Standard Deviation 11.156
Change From Baseline in Bone Turnover Markers at EOT (Up to 82 Months) EOT: P1NP	91.85 Microgram per liter (μg/L) Standard Deviation 104.327
Change From Baseline in Bone Turnover Markers at EOT (Up to 82 Months) EOT: Osteocalcin	10.06 Microgram per liter (μg/L) Standard Deviation 11.570

SECONDARY outcome

Timeframe: Baseline, EOT (up to 82 months)

Change form baseline in bone turnover marker (s-CTx)was reported. EOT was defined as the last determination of response or last available measurement during the treatment period.

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=47 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Change From Baseline in Serum Carboxy Terminal Telopeptide of Type I Collagen (s-CTx) Bone Turnover Marker at EOT (Up to 82 Months)	224.21 Nanogram per liter (ng/L) Standard Deviation 295.858

SECONDARY outcome

Timeframe: Baseline, Week 52 and EOT (up to 82 months)

Change from baseline in BMD of lumbar spine (L1-L4), hip-total, hip-trochanter, hip-intertrochanter, hip-ward's triangle, hip-femoral neck, distal one third radius at Week 52 then every 12 months until EOT were assessed by dual-energy X-ray absorptiometry \[DXA\] and Z-score. EOT was defined as the last determination of response or last available measurement during the treatment period.

Outcome measures

Outcome measures
Measure	rhPTH (1-84) n=49 Participants Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) Lumbar Spine (L1-L4) - Change at Week 52	-0.0156 gram per square centimeter (g/cm^2) Standard Deviation 0.0891
Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) Lumbar spine (L1-L4) - Change at EOT	-0.0272 gram per square centimeter (g/cm^2) Standard Deviation 0.1111
Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) Hip - Total - Change at Week 52	-0.0189 gram per square centimeter (g/cm^2) Standard Deviation 0.0572
Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) Hip - Total - Change at EOT	-0.0329 gram per square centimeter (g/cm^2) Standard Deviation 0.0747
Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) Hip - Femoral Neck - Change at Week 52	-0.0278 gram per square centimeter (g/cm^2) Standard Deviation 0.0553
Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) Hip - Femoral Neck - Change at EOT	-0.0364 gram per square centimeter (g/cm^2) Standard Deviation 0.0848
Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) Hip - Trochanter - Change at Week 52	-0.0235 gram per square centimeter (g/cm^2) Standard Deviation 0.0542
Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) Hip - Trochanter- Change at EOT	-0.0236 gram per square centimeter (g/cm^2) Standard Deviation 0.1018
Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) Hip - Ward's Triangle - Change at Week 52	-0.0081 gram per square centimeter (g/cm^2) Standard Deviation 0.0827
Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) Hip - Ward's Triangle - Change at EOT	-0.0178 gram per square centimeter (g/cm^2) Standard Deviation 0.1014
Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) Distal One Third Radius - Change at Week 52	-0.0006 gram per square centimeter (g/cm^2) Standard Deviation 0.0629
Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) Distal One Third Radius - Change at EOT	-0.0368 gram per square centimeter (g/cm^2) Standard Deviation 0.0895

Adverse Events

rhPTH(1-84)

Serious events: 13 serious events

Other events: 48 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	rhPTH(1-84) n=49 participants at risk Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Musculoskeletal and connective tissue disorders Back pain	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Biliary adenoma	2.0% 1/49 • Number of events 2 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma metastatic	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Gastrointestinal disorders Abdominal pain	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
General disorders Chest discomfort	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Cardiac disorders Cardiac arrest	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Cardiac disorders Cardiac failure congestive	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Bronchitis viral	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Cellulitis	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Gastroenteritis	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Groin abscess	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Sepsis	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Septic shock	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Subcutaneous abscess	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Viral infection	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Injury, poisoning and procedural complications Radius fracture	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Injury, poisoning and procedural complications Ulna fracture	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Renal and urinary disorders Calculus ureteric	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Hepatobiliary disorders Cholecystitis	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Hepatobiliary disorders Cholelithiasis	2.0% 1/49 • Number of events 2 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Metabolism and nutrition disorders Hypocalcaemia	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Nervous system disorders Syncope	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Respiratory, thoracic and mediastinal disorders Respiratory acidosis	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Respiratory, thoracic and mediastinal disorders Throat tightness	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Skin and subcutaneous tissue disorders Urticaria	2.0% 1/49 • Number of events 1 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.

Other adverse events

Other adverse events
Measure	rhPTH(1-84) n=49 participants at risk Participants received rhPTH (1-84) subcutaneous injection with a starting dose of 25 or 50 microgram (mcg) once daily with dose adjusted by the investigator with upwards in increments of 25 mcg up to 100 mcg daily, with the goal to achieve or maintain total serum calcium levels in the range of 8.0 to 9.0 milligrams per deciliter (mg/dL).
Blood and lymphatic system disorders Anaemia	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Blood and lymphatic system disorders Lymphadenopathy	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Arthralgia	26.5% 13/49 • Number of events 17 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Arthritis	8.2% 4/49 • Number of events 6 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Back pain	20.4% 10/49 • Number of events 15 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Bursitis	8.2% 4/49 • Number of events 4 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Joint swelling	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Muscle spasms	38.8% 19/49 • Number of events 42 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.1% 3/49 • Number of events 5 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Myalgia	12.2% 6/49 • Number of events 10 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Neck pain	8.2% 4/49 • Number of events 4 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Osteoarthritis	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Pain in extremity	20.4% 10/49 • Number of events 17 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Musculoskeletal and connective tissue disorders Tendonitis	8.2% 4/49 • Number of events 6 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Vascular disorders Hot flush	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Vascular disorders Hypertension	12.2% 6/49 • Number of events 6 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Ear and labyrinth disorders Vertigo	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Gastrointestinal disorders Abdominal discomfort	8.2% 4/49 • Number of events 4 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Gastrointestinal disorders Abdominal pain	8.2% 4/49 • Number of events 4 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Gastrointestinal disorders Colonic polyp	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Gastrointestinal disorders Constipation	20.4% 10/49 • Number of events 11 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Gastrointestinal disorders Diarrhoea	20.4% 10/49 • Number of events 11 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Gastrointestinal disorders Dyspepsia	10.2% 5/49 • Number of events 7 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Gastrointestinal disorders Nausea	30.6% 15/49 • Number of events 20 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Gastrointestinal disorders Paraesthesia oral	6.1% 3/49 • Number of events 5 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Gastrointestinal disorders Toothache	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Gastrointestinal disorders Vomiting	12.2% 6/49 • Number of events 6 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
General disorders Chest discomfort	10.2% 5/49 • Number of events 5 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
General disorders Fatigue	16.3% 8/49 • Number of events 13 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Cardiac disorders Palpitations	10.2% 5/49 • Number of events 5 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Immune system disorders Seasonal allergy	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Bronchitis	24.5% 12/49 • Number of events 16 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Cystitis	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Ear infection	10.2% 5/49 • Number of events 5 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Gastroenteritis viral	16.3% 8/49 • Number of events 12 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Herpes zoster	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Influenza	20.4% 10/49 • Number of events 11 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Nasopharyngitis	22.4% 11/49 • Number of events 22 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Sinusitis	32.7% 16/49 • Number of events 31 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Tooth infection	8.2% 4/49 • Number of events 5 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Upper respiratory tract infection	16.3% 8/49 • Number of events 11 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Infections and infestations Urinary tract infection	20.4% 10/49 • Number of events 14 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Injury, poisoning and procedural complications Ankle fracture	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Injury, poisoning and procedural complications Joint sprain	14.3% 7/49 • Number of events 7 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Injury, poisoning and procedural complications Meniscus lesion	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Injury, poisoning and procedural complications Muscle strain	12.2% 6/49 • Number of events 6 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Injury, poisoning and procedural complications Procedural pain	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Investigations Blood calcium decreased	14.3% 7/49 • Number of events 7 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Investigations Blood glucose increased	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Investigations Urine calcium increased	8.2% 4/49 • Number of events 9 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Investigations Vitamin D decreased	10.2% 5/49 • Number of events 5 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Renal and urinary disorders Hypercalciuria	10.2% 5/49 • Number of events 5 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Renal and urinary disorders Nephrolithiasis	12.2% 6/49 • Number of events 9 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Renal and urinary disorders Renal cyst	6.1% 3/49 • Number of events 4 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Metabolism and nutrition disorders Hypercalcaemia	16.3% 8/49 • Number of events 11 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Metabolism and nutrition disorders Hypocalcaemia	38.8% 19/49 • Number of events 50 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Metabolism and nutrition disorders Iron deficiency	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Metabolism and nutrition disorders Tetany	14.3% 7/49 • Number of events 40 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Metabolism and nutrition disorders Vitamin D deficiency	16.3% 8/49 • Number of events 8 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Nervous system disorders Dizziness	14.3% 7/49 • Number of events 8 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Nervous system disorders Headache	26.5% 13/49 • Number of events 22 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Nervous system disorders Hypoaesthesia	6.1% 3/49 • Number of events 4 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Nervous system disorders Migraine	8.2% 4/49 • Number of events 5 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Nervous system disorders Paraesthesia	30.6% 15/49 • Number of events 32 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Nervous system disorders Tremor	8.2% 4/49 • Number of events 5 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Psychiatric disorders Anxiety	14.3% 7/49 • Number of events 7 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Psychiatric disorders Depression	6.1% 3/49 • Number of events 3 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Psychiatric disorders Insomnia	10.2% 5/49 • Number of events 5 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Respiratory, thoracic and mediastinal disorders Cough	8.2% 4/49 • Number of events 4 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.1% 3/49 • Number of events 4 • From start of study drug administration up to follow-up (Up to 82 months) Safety population included all participants who received at least one dose of study drug with any follow-up information and differ from the started population.

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER